Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin (Retracted Article. See vol 282, pg 29067, 2007)
Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin (Retracted Article. See vol 282, pg 29067, 2007)
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DOI：
10.1074/jbc.m108319200
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发表时间：
2002-01-18
影响因子：
4.8
通讯作者：
Walsh, PN
中科院分区：
文献类型：
--
作者：
Baglia, FA;Badellino, KO;Walsh, PN
因子XI结合到受刺激的血小板表面的高亲和力位点，在那里它被凝血酶有效地激活。在这里，我们提供的证据表明，血小板上的因子XI结合位点位于GP Ib-IX-V复合物的糖蛋白（GP） Ibalpha亚基中，如下所示。1) Bernard-Soulier血小板缺乏该复合物，缺乏因子XI结合；2)两种GP α配体SZ-2（单克隆抗体）和牛血管性血友病因子抑制因子XI与血小板的结合；3)通过表面等离子体共振，因子XI以Zn2+依赖的方式特异性结合糖钙素（GP Iba的细胞外结构域）（K-d应用程序类似于52 nm）。然后，我们研究了糖钙素是否可以促进凝血酶（另一种GP α配体）激活因子XI。在高分子量激肽原（45纳米）、Zn2+和Ca2+离子存在下，凝血酶激活因子XI在糖钙蛋白存在下的速率与在硫酸葡聚糖存在下的速率相当（1杯/毫升）。在较高的高分子量激肽原浓度（360 nm）下，糖钙蛋白存在时凝血酶催化因子XI的活化率与活化血小板相当。因此，因子XI与GP Ib-IX-V复合物结合，促进其被凝血酶激活。
Factor XI binds to high affinity sites on the surface of stimulated platelets where it is efficiently activated by thrombin. Here, we provide evidence that the factor XI binding site on platelets is in the glycoprotein (GP) Ibalpha subunit of the GP Ib-IX-V complex as follows. 1) Bernard-Soulier platelets, lacking the complex, are deficient in factor XI binding; 2) two GP Ibalpha ligands, SZ-2 (a monoclonal antibody) and bovine von Willebrand factor, inhibit factor XI binding to platelets; 3) by surface plasmon resonance, factor XI bound specifically to glycocalicin (the extracellular domain of GP Iba) in Zn2+-dependent fashion (K-d app similar to 52 nm). We then investigated whether glycocalicin could promote factor XI activation by thrombin, another GP Ibalpha ligand. In the presence of high molecular weight kininogen (45 nm), Zn2+ and Ca2+ ions, thrombin activated factor XI in the presence of glycocalicin at rates comparable with those seen in the presence of dextran sulfate (1 mug/ml). With higher high molecular weight kininogen concentrations (360 nm), the rate of thrombin-catalyzed factor XI activation in the presence of glycocalicin was comparable with that on activated platelets. Thus, factor XI binds to the GP Ib-IX-V complex, promoting its activation by thrombin.